Search bioRxiv⌕ Search

Biology subjects

Lorenz, A.

Publications and source records attributed to Lorenz, A..

11 recordsLinked to original sources

Towards a multi-metric assessment of river restoration ecological outcomes across projects and contexts

The assessment of the ecological outcomes of river restoration projects remains a complex undertaking due to the high variability of responses observed. This variability is dependent on a number of factors, including the location of the site under study, the indicators and taxa utilised in the analysis. In this study, a multi-metric and multi-contextual approach was applied to analyse 62 river restoration projects located in France, Germany and the Netherlands. This methodological approach facilitated the characterisation of the responses exhibited by macroinvertebrate communities in response to restoration initiatives, and the subsequent identification of the environmental contexts and the categories of restoration measures that exerted influence on these responses. Utilising log-response ratios based on both taxonomic and functional ecological metrics, a k-means clustering analysis was performed. This analysis yielded two distinct groups of sites: the first exhibiting predominantly positive responses to restoration, and the second demonstrating neutral or marginally negative responses. Positive responses have been shown to be associated with ambitious restoration projects, which are characterised by measures targeting regional-scale processes. These measures include the implementation of projects designed to improve river longitudinal continuity in degraded catchment areas, where the density of obstacles and the intensity of agricultural use are particularly high. Conversely, restoration initiatives targeting local-scale issues within more natural contexts or at high altitude exhibited minimal to no ecological response. This study emphasises the significance of an integrated approach that incorporates various facets (taxonomic and functional) of biodiversity, along with a meticulous examination of the environmental context and project construction, to enhance the evaluation of the ecological benefits of river restoration. The findings of this study may also be applicable in the context of fieldwork, providing practitioners with a framework to inform the design of restoration projects.

ecology↗

Genetic Gains from Sixty Years of Spring Wheat Breeding in the Northern Plains of the US

Evaluating genetic gains over time is essential for assessing the success of breeding programs and refining strategies for ongoing improvement. Hard red spring (HRS) wheat is an important wheat class in the US and is primarily grown in the Northern Great Plains. Despite a long history of breeding efforts in this region, long-term quantification of genetic gains for key traits has remained limited. This study analyzes over sixty years of data from the USDA-coordinated Hard Red Spring Wheat Uniform Regional Nursery (HRSWURN) to evaluate genetic advancements in agronomic traits across multiple phases. A significant positive genetic gain of 0.61% per annum was observed for grain yield in HRS wheat released in the Northern US region, which is lower than the expected gains needed to meet future wheat demand. The change was 0.07% for test weight, -0.04% for days to heading, and -0.16% for plant height. Notably, sustained yield improvements have not affected grain protein levels since they were first measured in 1995, indicating that ongoing selection has effectively balanced grain yield and protein despite their negative correlation (r = -0.31). Assessment of genetic gains over 20-year phases suggested slowing rates of genetic gains for grain yield but did not indicate any plateaus. The realized genetic gains were generally higher for individual breeding programs when breeding for target environments, with the public breeding program in Minnesota observing gains of approximately 1% per annum. These findings highlight the significant impact of long-term breeding efforts and offer valuable insights for refining future breeding strategies.

plant biology↗

In vitro evolution of caspofungin resistance in Candidozyma auris via FKS1 hotspot I mutations results in moderate fitness trade-offs but no reduction in virulence

Resistance to echinocandins in the recently emerged pathogen Candidozyma auris (previously known as Candida auris) poses significant clinical challenges. This study reports the in vitro evolution of a caspofungin-sensitive C. auris clade II isolate to acquire caspofungin resistance. We sequenced the whole genome of the parental strain and its drug-resistant progeny. The resistant isolates harboured mutations in the FKS1 gene altering a conserved residue (S639) also mutated in caspofungin-resistant clinical isolates; demonstrating that FKS1-S639 mutations are sufficient to confer resistance to caspofungin. Using these resistant strains, we examined cross-resistance & collateral sensitivity to other antifungal drugs and to cell wall stress, cell wall ultrastructure, biofilm formation, and virulence. As expected, both FKS1-S639P and FKS1-S639Y variants exhibited resistance not only to caspofungin but also to other echinocandins. Interestingly, these resistant strains showed moderate collateral sensitivity to certain azole antifungals and increased susceptibility to cell wall stress. While cell wall chitin content was slightly elevated in resistant isolates compared to sensitive ones, overall cell wall structure and phosphomannan levels remained unchanged. Biofilm formation capabilities were similar across all strains, and virulence in invertebrate models was unaffected by the FKS1 mutations. These findings indicate that while the evolution of caspofungin resistance through FKS1 mutations does incur fitness trade-offs, it does not substantially compromise the pathogenic potential of C. auris. This underscores the complexities of evolution of antifungal resistance mechanisms in this pathogen and the impact on its biology.

microbiology↗

Assembly, comparative analysis, and utilization of a single haplotype reference genome for soybean

Cultivar Williams 82 has served as the reference genome for the soybean research community since 2008, but is known to have areas of genomic heterogeneity among different sub-lines. This work provides an updated assembly (version Wm82.a6) derived from a specific sub-line known as Wm82-ISU-01 (seeds available under USDA accession PI 704477). The genome was assembled using Pacific BioSciences HiFi reads and integrated into chromosomes using HiC. The 20 soybean chromosomes assembled into a genome of 1.01Gb, consisting of 36 contigs. The genome annotation identified 48,387 gene models, named in accordance with previous assembly versions Wm82.a2 and Wm82.a4. Comparisons of Wm82.a6 with other near-gapless assemblies of Williams 82 reveal large regions of genomic heterogeneity, including regions of differential introgression from the genotype Kingwa within approximately 30 Mb and 25 Mb segments on chromosomes 03 and 07, respectively. Additionally, our analysis revealed a previously unknown large ([~]20 Mb) heterogeneous region in the pericentromeric region of chromosome 12, where Wm82.a6 matches the Williams haplotype while the other two near-gapless assemblies do not match the haplotype of either parent of Williams 82. In addition to the Wm82.a6 assembly, we also assembled the genome of soybean line Fiskeby III, a rich resource for abiotic stress resistance genes. A genome comparison of Wm82.a6 with Fiskeby III revealed the nucleotide and structural polymorphisms between the two genomes within a QTL region for iron deficiency chlorosis resistance. The Wm82.a6 and Fiskeby III genomes described here will enhance comparative and functional genomics capacities and applications in the soybean community.

plant biology↗

Candida auris undergoes adhesin-dependent and -independent cellular aggregation

Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies. Epidemiological and genomic studies have identified five geographical clades (I-V), which display phenotypic and genomic differences. Aggregation of cells, a phenotype primarily of clade III strains, has been linked to reduced virulence in mouse and Galleria mellonella infection models. The aggregation phenotype has thus been associated with conferring an advantage for (skin) colonisation rather than for systemic infection. However, strains with different clade affiliations were compared to infer the effects of different morphologies on virulence. This makes it difficult to distinguish morphology-dependent causes from clade-specific or even strain-specific genetic factors. Here, we identify two different types of aggregation: one induced by antifungal treatment which is a result of a cell separation defect; and a second which is controlled by growth conditions and only occurs in strains with the ability to aggregate. The latter aggregation type depends on an ALS-family adhesin which is differentially expressed during aggregation in an aggregative C. auris strain. Finally, we demonstrate that macrophages cannot clear aggregates, suggesting that aggregation might after all provide a benefit during systemic infection and could facilitate long-term persistence in the host. Author SummaryCandida auris is a single-celled fungus, a yeast, that can cause severe infections in hospital patients. This fungus is difficult to treat because it is resistant to many antifungal drugs. Therefore, to understand the processes that enhance the virulence of this yeast with a view to developing new treatments. Previous studies have found that C. auris can form aggregates, or clumps of cells, which may play a role in how the fungus infects people. In this study, we identified two different types of aggregation in C. auris, one triggered by antifungal treatment, and another controlled by growth conditions. This discovery allowed us to study aggregate formation in the same genetic background. In doing so, we found that a certain protein, an ALS-family adhesin, is involved in the aggregation process. Surprisingly, we also discovered that aggregates may promote infection by making it harder for the immune system to clear the yeast. This new understanding could help researchers develop better ways to fight C. auris infections.

microbiology↗

Concerted but segregated actions of oxytocin and vasopressin within the ventral and dorsal lateral septum determine female aggression

In contrast to males, aggression in females has been rarely studied. Here, we established a rat model of enhanced female aggression using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialyses approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), are required for female aggression. Accordingly, increased excitability of OXT-responsive neurons in the vLS and decreased excitability of AVP-responsive neurons in the dLS were essential to evoke female aggression. Finally, in vitro activation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data demonstrate that septal release of OXT and AVP affects female aggression by differential regulation of the excitatory-inhibitory balance within subnetworks of the LS.

neuroscience↗

Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint

The morphogenetic switching between yeast cells and filaments (true hyphae and pseudohyphae) is a key cellular feature required for full virulence in many polymorphic fungal pathogens, such as Candida albicans. In the recently emerged yeast pathogen Candida auris, occasional elongation of cells has been reported. However, environmental conditions and genetic triggers for filament formation have remained elusive. Here, we report that induction of DNA damage and perturbation of replication forks by treatment with genotoxins, such as hydroxyurea, methyl methanesulfonate, and the clinically relevant fungistatic 5-fluorocytosine, causes filamentation in C. auris. The filaments formed were characteristic of pseudohyphae and not parallel-sided true hyphae. Pseudohyphal growth is apparently signalled through the S phase checkpoint and, interestingly, is Tup1-independent in C. auris. Intriguingly, the morphogenetic switching capability is strain-specific in C. auris, highlighting the heterogenous nature of the species as a whole.\n\nIMPORTANCECandida auris is a newly emerged fungal pathogen of humans. This species was first reported in 2009, when it was identified in an ear infection of a patient in Japan. However, despite intense interest in this organism as an often multidrug-resistant fungus there is little knowledge about its cellular biology. During infection of human patients, fungi are able to change cell shape from ellipsoidal yeast cells to elongated filaments to adapt to various conditions within the host organism. There are different types of filaments, which are triggered by reactions to different cues. Candida auris fails to form filaments when exposed to triggers that stimulate yeast-filament morphogenesis in other fungi. Here, we show that it does form filaments when its DNA is damaged. These conditions might arise when Candida auris cells interact with host immune cells, or growing in certain host tissues (kidney, bladder), or during treatment with antifungal drugs.

microbiology↗

DNA sequence differences and temperature are determinants of meiotic recombination outcome

Meiotic recombination is essential for producing healthy gametes, and also generates genetic diversity. DNA double-strand break (DSB) formation is the initiating step of meiotic recombination, producing, among other outcomes, crossovers between homologous chromosomes (homologs), which provide physical links to guide accurate chromosome segregation. The parameters influencing DSB position and repair are thus crucial determinants of reproductive success and genetic diversity. Using Schizosaccharomyces pombe, we show that the distance between sequence polymorphisms across homologs has a strong impact on meiotic recombination rate. The closer the sequence polymorphisms are to each other across the homologs the fewer recombination events were observed. In the immediate vicinity of DSBs, sequence polymorphisms affect the frequency of intragenic recombination events (gene conversions). Additionally, and unexpectedly, the crossover rate of flanking markers tens of kilobases away from the sequence polymorphisms was affected by their relative position to each other amongst the progeny having undergone intragenic recombination. A major regulator of this distance-dependent effect is the MutS-MutL complex consisting of Msh2, Msh6, Mlh1, and Pms1. Additionally, the DNA helicases Rqh1 and Fml1 shape recombination frequency, although the effects seen here are largely independent of the relative position of the sequence polymorphisms.\n\nPreambleDue to a mistake during analysis of a batch of Sanger sequencing reactions for Supplementary Figure S1, we erroneously stated that we found evidence for intragenic crossovers. We now show that intragenic crossovers are less likely than we initially thought. We sincerely apologize for our mishap and any inconvenience it might have caused. However, this does not affect the main conclusions of our paper, just how some of our results are interpreted. This new manuscript version has been amended accordingly.

genetics↗

Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates

Candida auris is a newly emerging pathogenic microbe, having been identified as a medically relevant fungus as recently as 2009. It is the most drug-resistant yeast species known to date and its emergence and population structure are unusual. Because of its recent emergence we are largely ignorant about fundamental aspects of its general biology, life cycle, and population dynamics. Here we report the karyotype variability of 26 C. auris strains representing the four main clades. We demonstrate that all strains are haploid and have a highly plastic karyotype containing five to seven chromosomes, which can undergo marked alterations within a short time-frame when the fungus is put under genotoxic, heat, or osmotic stress. No simple correlation was found between karyotype pattern, drug resistance, and clade affiliation indicating that karyotype heterogeneity is rapidly evolving. As with other Candida species, these marked karyotype differences between isolates are likely to have an important impact on pathogenic traits of C. auris.

microbiology↗

Immediate visualization of recombination events and chromosome segregation defects in fission yeast meiosis

Schizosaccharomyces pombe, also known as fission yeast, is an established model for studying chromosome biological processes. Over the years research employing fission yeast has made important contributions to our knowledge about chromosome segregation during meiosis, as well as meiotic recombination and its regulation. Quantification of meiotic recombination frequency is not a straightforward undertaking, either requiring viable progeny for a genetic plating assay, or relying on laborious Southern blot analysis of recombination intermediates. Neither of these methods lends itself to high-throughput screens to identify novel meiotic factors. Here, we establish visual assays novel to Sz. pombe for characterizing chromosome segregation and meiotic recombination phenotypes. Genes expressing red, yellow, and/or cyan fluorophores from spore-autonomous promoters have been integrated into the fission yeast genomes, either close to the centromere of chromosome I to monitor chromosome segregation, or on the arm of chromosome III to form a genetic interval at which recombination frequency can be determined. The visual recombination assay allows straightforward and immediate assessment of the genetic outcome of a single meiosis by epi-fluorescence microscopy without requiring tetrad dissection. We also demonstrate that the recombination frequency analysis can be automatized by utilizing imaging flow cytometry to enable high-throughput screens. These assays have several advantages over traditional methods for analysing meiotic phenotypes.

genetics↗

Genetic interactions between the chromosome axis-associated protein Hop1 and homologous recombination determinants in Schizosaccharomyces pombe

Hop1 is a component of the meiosis-specific chromosome axis and belongs to the evolutionarily conserved family of HORMA domain proteins. Hop1 and its orthologs in higher eukaryotes are a major factor in promoting double-strand DNA break formation and inter-homolog recombination. In budding yeast and mammals they are also involved in a meiotic checkpoint kinase cascade monitoring the completion of double-strand DNA break repair. We used the fission yeast, Schizosaccharomyces pombe, which lacks a canonical synaptonemal complex to test whether Hop1 has a role beyond supporting the generation of double-strand DNA breaks and facilitating inter-homolog recombination events. We determined how mutants of homologous recombination factors genetically interact with hop1, studied the role(s) of the HORMA domain of Hop1, and characterized a bio-informatically predicted interactor of Hop1, Aho1 (SPAC688.03c). Our observations indicate that in fission yeast, Hop1 does require its HORMA domain to support wild-type levels of meiotic recombination and localization to meiotic chromatin. Furthermore, we show that hop1{Delta} only weakly interacts genetically with mutants of homologous recombination factors, and in fission yeast likely has no major role beyond break formation and promoting inter-homolog events. We speculate that after the evolutionary loss of the synaptonemal complex, Hop1 likely has become less important for modulating recombination outcome during meiosis in fission yeast, and that this led to a concurrent rewiring of genetic pathways controlling meiotic recombination.

genetics↗